Molecular biomedicine最新文献

Applications of gene pair methods in clinical research: advancing precision medicine. 基因对方法在临床研究中的应用：推进精准医学。

IF 6.3

Molecular biomedicine Pub Date : 2025-04-09 DOI: 10.1186/s43556-025-00263-w

Changchun Wu, Xueqin Xie, Xin Yang, Mengze Du, Hao Lin, Jian Huang

{"title":"Applications of gene pair methods in clinical research: advancing precision medicine.","authors":"Changchun Wu, Xueqin Xie, Xin Yang, Mengze Du, Hao Lin, Jian Huang","doi":"10.1186/s43556-025-00263-w","DOIUrl":"https://doi.org/10.1186/s43556-025-00263-w","url":null,"abstract":"The rapid evolution of high-throughput sequencing technologies has revolutionized biomedical research, producing vast amounts of gene expression data that hold immense potential for biological discovery and clinical applications. Effectively mining these large-scale, high-dimensional data is crucial for facilitating disease detection, subtype differentiation, and understanding the molecular mechanisms underlying disease progression. However, the conventional paradigm of single-gene profiling, measuring absolute expression levels of individual genes, faces critical limitations in clinical implementation. These include vulnerability to batch effects and platform-dependent normalization requirements. In contrast, emerging approaches analyzing relative expression relationships between gene pairs demonstrate unique advantages. By focusing on binary comparisons of two genes' expression magnitudes, these methods inherently normalize experimental variations while capturing biologically stable interaction patterns. In this review, we systematically evaluate gene pair-based analytical frameworks. We classify eleven computational approaches into two fundamental categories: expression value-based methods quantifying differential expression patterns, and rank-based methods exploiting transcriptional ordering relationships. To bridge methodological development with practical implementation, we establish a reproducible analytical pipeline incorporating feature selection, classifier construction, and model evaluation modules using real-world benchmark datasets from pulmonary tuberculosis studies. These findings position gene pair analysis as a transformative paradigm for mining high-dimensional omics data, with direct implications for precision biomarker discovery and mechanistic studies of disease progression.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"22"},"PeriodicalIF":6.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Telocyte-derived exosomes promote angiogenesis and alleviate acute respiratory distress syndrome via JAK/STAT-miR-221-E2F2 axis. 远端细胞来源的外泌体通过JAK/STAT-miR-221-E2F2轴促进血管生成，缓解急性呼吸窘迫综合征。

IF 6.3

Molecular biomedicine Pub Date : 2025-04-08 DOI: 10.1186/s43556-025-00259-6

Rongrong Gao, Xu Zhang, Huihui Ju, Yile Zhou, Luoyue Yin, Liuke Yang, Pinwen Wu, Xia Sun, Hao Fang

{"title":"Telocyte-derived exosomes promote angiogenesis and alleviate acute respiratory distress syndrome via JAK/STAT-miR-221-E2F2 axis.","authors":"Rongrong Gao, Xu Zhang, Huihui Ju, Yile Zhou, Luoyue Yin, Liuke Yang, Pinwen Wu, Xia Sun, Hao Fang","doi":"10.1186/s43556-025-00259-6","DOIUrl":"https://doi.org/10.1186/s43556-025-00259-6","url":null,"abstract":"Acute respiratory distress syndrome (ARDS) is characterized by severe respiratory failure and significant inflammation, leading to vascular and epithelial cell damage. The absence of effective pharmacologic treatments underscores the need for novel therapeutic approaches. Telocytes (TCs), a newly identified type of interstitial cells, have shown potential in tissue repair and angiogenesis, particularly through the release of exosomal microRNAs (miRNAs). Exosomes were isolated from LPS (lipopolysaccharide)-stimulated TCs and characterized using western blotting and nanoparticle tracking analysis. The role of exosomal miR-221 in angiogenesis was assessed through tube formation, migration, and proliferation assays in mouse vascular endothelial cells (MVECs). The JAK/STAT pathway's involvement in miR-221 regulation was determined using western blotting and qRT-PCR. A dual-luciferase assay confirmed E2F2 as a direct target of miR-221. ARDS mouse model was established via LPS instillation, and the therapeutic effects of TCs-derived exosomes were evaluated by histopathological scoring, cytokine analysis, and endothelial barrier integrity assays. Our findings demonstrated that exosomes from LPS-stimulated TCs significantly promoted angiogenesis, proliferation, and migration in MVECs. These effects were mediated by miR-221, which downregulated E2F2 expression, an important regulator of endothelial cell functions. The JAK/STAT pathway played a crucial role in miR-221 production, with pathway inhibition reducing miR-221 levels and attenuating its pro-angiogenic effects. In vivo, TCs-derived exosomes reduced lung inflammation and tissue damage in ARDS mice, effects that were reversed by miR-221 inhibition. These results suggested that TCs-derived exosomes promoted angiogenesis and alleviated ARDS through the JAK/STAT-miR-221-E2F2 axis.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"21"},"PeriodicalIF":6.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer metastasis: molecular mechanisms and therapeutic interventions. 癌症转移：分子机制和治疗干预。

IF 6.3

Molecular biomedicine Pub Date : 2025-04-07 DOI: 10.1186/s43556-025-00261-y

Xiaofeng Dai, Ming Xi, Jitian Li

{"title":"Cancer metastasis: molecular mechanisms and therapeutic interventions.","authors":"Xiaofeng Dai, Ming Xi, Jitian Li","doi":"10.1186/s43556-025-00261-y","DOIUrl":"10.1186/s43556-025-00261-y","url":null,"abstract":"The metastatic cascade is a complicated process where cancer cells travel across multiple organs distant from their primary site of onset. Despite the wide acceptance of the 'seed and soil' theory, mechanisms driving metastasis organotropism remain mystery. Using breast cancer of different subtypes as the disease model, we characterized the 'metastatic profile of cancer cells' and the 'redox status of the organ microenvironment' as the primary determinants of cancer metastasis organotropism. Mechanically, we identified a positive correlation between cancer metabolic plasticity and stemness, and proposed oxidative stress as the selection power of cancer cells succeeding the metastasis cascade. Therapeutically, we proposed the use of pro-oxidative therapeutics in ablating cancer cells taking advantages of this fragile moment during metastasis. We comprehensively reviewed current pro-oxidative strategies for treating cancers that cover the first line chemo- and radio-therapies, approaches relying on naturally existing power including magnetic field, electric field, light and sound, nanoparticle-based anti-cancer composites obtained through artificial design, as well as cold atmospheric plasma as an innovative pro-oxidative multi-modal modality. We discussed possible combinations of pro-oxidative approaches with existing therapeutics in oncology prior to the forecast of future research directions. This paper identified the fundamental mechanics driving metastasis organotropism and proposed intervention strategies accordingly. Insights provided here may offer clues for the design of innovative solutions that may open a new paradigm for cancer treatment.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"20"},"PeriodicalIF":6.3,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases. Klotho抗衰老蛋白：分子机制及其在疾病中的治疗潜力。

IF 6.3

Molecular biomedicine Pub Date : 2025-03-22 DOI: 10.1186/s43556-025-00253-y

Aditya Dipakrao Hajare, Neha Dagar, Anil Bhanudas Gaikwad

{"title":"Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.","authors":"Aditya Dipakrao Hajare, Neha Dagar, Anil Bhanudas Gaikwad","doi":"10.1186/s43556-025-00253-y","DOIUrl":"10.1186/s43556-025-00253-y","url":null,"abstract":"Klotho, initially introduced as an anti-aging protein, is expressed in the brain, pancreas, and most prominently in the kidney. The two forms of Klotho (membrane-bound and soluble form) have diverse pharmacological functions such as anti-inflammatory, anti-oxidative, anti-fibrotic, tumour-suppressive etc. The membrane-bound form plays a pivotal role in maintaining kidney homeostasis by regulating fibroblast growth factor 23 (FGF 23) signalling, vitamin D metabolism and phosphate balance. Klotho deficiency has been linked with significantly reduced protection against various kidney pathological phenotypes, including diabetic kidney disease (DKD), which is a major cause of chronic kidney disease leading to end-stage kidney disease. Owing to the pleiotropic actions of klotho, it has shown beneficial effects in DKD by tackling the complex pathophysiology and reducing kidney inflammation, oxidative stress, as well as fibrosis. Moreover, the protective effect of klotho extends beyond DKD in other pathological conditions, including cardiovascular diseases, alzheimer's disease, cancer, inflammatory bowel disease, and liver disease. Therefore, this review summarizes the relationship between Klotho expression and various diseases with a special emphasis on DKD, the distinct mechanisms and the potential of exogenous Klotho supplementation as a therapeutic strategy. Future research into exogenous Klotho could unravel novel treatment avenues for DKD and other diseases.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"19"},"PeriodicalIF":6.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liquid biopsies in cancer. 癌症的液体活检。

IF 6.3

Molecular biomedicine Pub Date : 2025-03-20 DOI: 10.1186/s43556-025-00257-8

Hang Yin, Manjie Zhang, Yu Zhang, Xuebing Zhang, Xia Zhang, Bin Zhang

{"title":"Liquid biopsies in cancer.","authors":"Hang Yin, Manjie Zhang, Yu Zhang, Xuebing Zhang, Xia Zhang, Bin Zhang","doi":"10.1186/s43556-025-00257-8","DOIUrl":"10.1186/s43556-025-00257-8","url":null,"abstract":"Cancer ranks among the most lethal diseases worldwide. Tissue biopsy is currently the primary method for the diagnosis and biological analysis of various solid tumors. However, this method has some disadvantages related to insufficient tissue specimen collection and intratumoral heterogeneity. Liquid biopsy is a noninvasive approach for identifying cancer-related biomarkers in peripheral blood, which allows for repetitive sampling across multiple time points. In the field of liquid biopsy, representative biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Many studies have evaluated the prognostic and predictive roles of CTCs and ctDNA in various solid tumors. Although these studies have limitations, the results of most studies appear to consistently demonstrate the correlations of high CTC counts and ctDNA mutations with lower survival rates in cancer patients. Similarly, a reduction in CTC counts throughout therapy may be a potential prognostic indicator related to treatment response in advanced cancer patients. Moreover, the biochemical characteristics of CTCs and ctDNA can provide information about tumor biology as well as resistance mechanisms against targeted therapy. This review discusses the current clinical applications of liquid biopsy in cancer patients, emphasizing its possible utility in outcome prediction and treatment decision-making.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"18"},"PeriodicalIF":6.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

M6A-modified BFSP1 induces aerobic glycolysis to promote liver cancer growth and metastasis through upregulating tropomodulin 4. m6a修饰的BFSP1通过上调原调节蛋白4诱导有氧糖酵解促进肝癌生长和转移。

IF 6.3

Molecular biomedicine Pub Date : 2025-03-18 DOI: 10.1186/s43556-025-00256-9

Rong Li, Shunle Li, Lin Shen, Junhui Li, Di Zhang, Jinmin Yu, Lanxuan Huang, Na Liu, Hongwei Lu, Meng Xu

{"title":"M6A-modified BFSP1 induces aerobic glycolysis to promote liver cancer growth and metastasis through upregulating tropomodulin 4.","authors":"Rong Li, Shunle Li, Lin Shen, Junhui Li, Di Zhang, Jinmin Yu, Lanxuan Huang, Na Liu, Hongwei Lu, Meng Xu","doi":"10.1186/s43556-025-00256-9","DOIUrl":"10.1186/s43556-025-00256-9","url":null,"abstract":"RNA N6-methyladenosine (m6A) is a common RNA modification in eukaryotes, and its abnormal regulation is closely related to cancer progression. Aerobic glycolysis is a main way for cancer cells to obtain energy. It was found that beaded filament structural protein 1 (BFSP1) is a m6A related gene in liver cancer. However, the effect of m6A-modified BFSP1 on aerobic glycolysis and how it is regulated in liver cancer progression have not been explored. Here, we found that BFSP1 was upregulated in liver cancer cells and tissues. Overexpression of BFSP1 promoted the viability, invasion, and aerobic glycolysis of liver cancer cells, whereas knockdown of BFSP1 showed the opposite effects. Co-immunoprecipitation, immunofluorescence and GST pull down analyses showed that BFSP1 directly interacted with tropomodalin 4 (TMOD4), and knockdown of TMOD4 reversed BFSP1 overexpression-induced malignant phenotypes and aerobic glycolysis in liver cancer cells. Moreover, methyltransferase-like 3 (METTL3) enhanced BFSP1 stability by augmenting m6A modification of BFSP1 mRNA, which is achieved in a YTHDF1-dependent manner. In vivo experiments in mice confirmed that METTL3 increased BFSP1 stability by promoting m6A modification of BFSP1 mRNA, and knockdown of BFSP1 inhibited tumor growth and metastasis. In summary, METTL3-mediated m6A methylation of BFSP1 mRNA plays an important role in the aerobic glycolysis and progression of liver cancer, providing a potential therapeutic strategy for liver cancer.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"17"},"PeriodicalIF":6.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel neuroprotective mechanism of selegiline by suppressing the pro-apoptotic activity of protein disulfide isomerase. selegiline抑制蛋白二硫异构酶促凋亡活性的神经保护新机制。

IF 6.3

Molecular biomedicine Pub Date : 2025-03-17 DOI: 10.1186/s43556-025-00255-w

Yuting Xie, Bing Chen, Piao Luo, Jingnan Huang, Jigang Wang, Jichao Sun, Zhen Liang

引用次数: 0

Correction: A promising mRNA vaccine derived from the JN.1 spike protein confers protective immunity against multiple emerged Omicron variants. 更正：从JN.1刺突蛋白衍生的mRNA疫苗很有前景，可对多种出现的Omicron变体产生保护性免疫。

IF 6.3

Molecular biomedicine Pub Date : 2025-03-17 DOI: 10.1186/s43556-025-00260-z

Danyi Ao, Dandan Peng, Cai He, Chunjun Ye, Weiqi Hong, Xiya Huang, Yishan Lu, Jie Shi, Yu Zhang, Jian Liu, Xiawei Wei, Yuquan Wei

引用次数: 0

Regulation of histone H3K27 methylation in inflammation and cancer. 组蛋白H3K27甲基化在炎症和癌症中的调控。

IF 6.3

Molecular biomedicine Pub Date : 2025-03-05 DOI: 10.1186/s43556-025-00254-x

Jing Ma, Yalin Zhang, Jingyuan Li, Yanqi Dang, Dan Hu

{"title":"Regulation of histone H3K27 methylation in inflammation and cancer.","authors":"Jing Ma, Yalin Zhang, Jingyuan Li, Yanqi Dang, Dan Hu","doi":"10.1186/s43556-025-00254-x","DOIUrl":"10.1186/s43556-025-00254-x","url":null,"abstract":"Inflammation is a multifaceted defense mechanism of the immune system against infection. Chronic inflammation is intricately linked to all stages of tumorigenesis and is therefore associated with an elevated risk of developing serious cancers. Epigenetic mechanisms have the capacity to trigger inflammation as well as facilitate tumor development and transformation within an inflammatory context. They achieve this by dynamically modulating the expression of both pro-inflammatory and anti-inflammatory cytokines, which in turn sustains chronic inflammation. The aberrant epigenetic landscape reconfigures the transcriptional programs of inflammatory and oncogenic genes. This reconfiguration is pivotal in dictating the biological functions of both tumor cells and immune cells. Aberrant histone H3 lysine 27 site (H3K27) methylation has been shown to be involved in biological behaviors such as inflammation development, tumor progression, and immune response. The establishment and maintenance of this repressive epigenetic mark is dependent on the involvement of the responsible histone modifying enzymes enhancer of zeste homologue 2 (EZH2), jumonji domain containing 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat gene X (UTX) as well as multiple cofactors. In addition, specific pharmacological agents have been shown to modulate H3K27 methylation levels, thereby modulating inflammation and carcinogenesis. This review comprehensively summarises the current characteristics and clinical significance of epigenetic regulation of H3K27 methylation in the context of inflammatory response and tumor progression.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"14"},"PeriodicalIF":6.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A promising mRNA vaccine derived from the JN.1 spike protein confers protective immunity against multiple emerged Omicron variants. 一种由JN.1刺突蛋白衍生的mRNA疫苗有望对多种出现的Omicron变体产生保护性免疫。

IF 6.3

Molecular biomedicine Pub Date : 2025-03-04 DOI: 10.1186/s43556-025-00258-7

Danyi Ao, Dandan Peng, Cai He, Chunjun Ye, Weiqi Hong, Xiya Huang, Yishan Lu, Jie Shi, Yu Zhang, Jian Liu, Xiawei Wei, Yuquan Wei

{"title":"A promising mRNA vaccine derived from the JN.1 spike protein confers protective immunity against multiple emerged Omicron variants.","authors":"Danyi Ao, Dandan Peng, Cai He, Chunjun Ye, Weiqi Hong, Xiya Huang, Yishan Lu, Jie Shi, Yu Zhang, Jian Liu, Xiawei Wei, Yuquan Wei","doi":"10.1186/s43556-025-00258-7","DOIUrl":"10.1186/s43556-025-00258-7","url":null,"abstract":"Despite the declared end of the COVID-19 pandemic, SARS-CoV-2 continues to evolve, with emerging JN.1-derived subvariants (e.g., KP.2, KP.3) compromising the efficacy of current XBB.1.5-based vaccines. To address this, we developed an mRNA vaccine encoding the full-length spike protein of JN.1, incorporating GSAS and 2P mutations and encapsulated in lipid nanoparticles (LNPs). The JN.1-mRNA vaccine elicited robust humoral and cellular immune responses in mice, including high JN.1-specific IgG titers, cross-neutralizing antibodies, and increased T follicular helper (Tfh) cells, germinal center (GC) B cells, and T cell cytokines. Importantly, immunity persisted for up to six months and induced RBD-specific long-lived plasma cells. We also compared the immune responses induced by homologous and heterologous vaccination regimens, and our results demonstrated that the heterologous regimen-combining JN.1-mRNA with a recombinant protein vaccine (RBDJN.1-HR)-induced stronger responses. These findings highlight the JN.1-mRNA vaccine constitutes an effective prophylactic approach against JN.1-related variants, as it induces potent neutralizing antibody responses across all tested lineages. This enhanced immunogenicity is expected to significantly reduce hospitalization rates and mitigate post-COVID complications associated with JN.1 and KP.3 infections. This study emphasizes the need for timely vaccine updates and the adaptability of mRNA vaccines in addressing emerging pathogens, providing a framework for combating future infectious diseases. Collectively, these results offer critical insights for vaccine design and public health strategies in response to emerging SARS-CoV-2 variants.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"6 1","pages":"13"},"PeriodicalIF":6.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0